PRODRUGS PDD UNIT 5 ANSARI AASHIF RAZA MOHD IMTIYAZ.pptx

PRODRUGS

1. SUBJECT : Principle of drug discovery. TOPIC : PRODRUG DESIGN. ANSARI AASHIF RAZA MOHD IMTIYAZ ( IInd semester , M.PHARM) DEPARTMENT OF PHARMACOLOGY 1 YEAR M PHARM ANSARI AASHIF RAZA 1

2. Prodrugs are medications that turn into an active form once they enter the body. Prodrugs help improve A medication's effectiveness. They may also be designed to avoid certain side effects or toxicities. The term prodrug relates to “biologically inert derivatives of drug molecules that undergo an enzymatic and/or chemical conversion in vivo to release the pharmacologically active parent drug.” 1 YEAR M PHARM ANSARI AASHIF RAZA 2 DEFINITION :

3. INTRODUCTION Almost all drugs possess some undesirable physicochemical and biological properties. Drug candidates are often discontinued due to issues of poor pharmacokinetic properties or high toxicities Their therapeutic efficacy can be improved by eliminating the undesirable properties while retaining the desirable ones. This can be achieved through biological, physical or chemical means. 1 YEAR M PHARM ANSARI AASHIF RAZA 3

4. The Biological approach is to alter the route of administration which may or may not be acceptable to the patient. The Physical approach is to modify the design of dosage forms such as controlled drug delivery of the drug. The best approach to enhancing drug selectivity while minimizing toxicity, is the chemical approach for the design of prodrugs. 1 YEAR M PHARM ANSARI AASHIF RAZA 4

5. Objectives of Prodrug Design There are three basic, overlapping objectives in prodrug research: 1. Pharmaceutical Objectives: To improve solubility, chemical stability, and organoleptic properties To decrease irritation and/or pain after local administration, To reduce problems related to the pharmaceutical technology of the active agent. 1 YEAR M PHARM ANSARI AASHIF RAZA 5

6. 2. Pharmacokinetic Objectives: To improve absorption (oral and by non-oral routes). To decrease presystemic metabolism to improve time profile To increase organ/ tissue-selective delivery of the active agent . 3. Pharmacodynamic Objectives: To decrease toxicity and improve therapeutic index. To design single chemical entities combining two drugs (co-drugs strategy. 1 YEAR M PHARM ANSARI AASHIF RAZA 6

7. Prodrug concept The awareness that the onset, intensity, and duration of drug action are greatly affected by the physicochemical properties of the drug has promoted the emergence of various prodrugs. Most of the limitations can be overcome by the prodrug approach, but after overcoming the various barriers, the prodrug should rapidly convert into active moiety after reaching the target site. The design of an efficient, stable, safe, acceptable and aesthetic way to target a drug to its site of action while overcoming various physical, chemical, and social barriers is certainly the utilization of the prodrug approach holds great potential. 1 YEAR M PHARM ANSARI AASHIF RAZA 7

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14. Site specific drug delivery After its absorption into the systemic circulation, the drug is distributed to the various parts of the body including the target site as well as the non-target tissue. These problems can be overcome by targeting the drug specifically to its site of action by prodrug design The prodrug is converted into its active form only in the target organ/tissue by utilizing either specific enzymes or a pH value different from the normal pH for activation e.g. 5- amino-salicylic acid. Tumor cells contain a higher concentration of phosphates and amidases than do normal cells. Consequently, a prodrug of cytotoxic agent could be directed to tumor cells if either of these enzymes was important to the prodrug activation process. Diethylstilbestrol diphosphate was designed for site-specific delivery of diethylstilbestrol to prostatic carcinoma tissue. 1 YEAR M PHARM ANSARI AASHIF RAZA 14

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